Inhibition of Osteoblast Functions by IKK/NF-κB in Osteoporosis

An imbalance in bone formation relative to bone resorption results in the net bone loss in osteoporosis and inflammatory bone diseases. While it is well known how bone resorption is stimulated, the molecular mechanisms that mediate impaired bone formation are poorly understood. Here we show that the time- and stage-specific inhibition of endogenous IκB kinase (IKK)/nuclear factor-kappa B (NF-κB) NF-κB in differentiated osteoblasts significantly increases trabecular bone mass and bone mineral density without affecting osteoclast activities in young mice. Moreover, the inhibition of IKK/NF-κB in differentiated osteoblasts maintains bone formation, thereby preventing osteoporotic bone loss induced by ovariectomy (OVX) in adult mice. The inhibition of IKK/NF-κB enhances the expression of Fra-1, an essential factor for bone matrix formation in vitro and in vivo. Taken together, our results suggest that targeting IKK/NF-κB may help to promote bone formation in the treatment of osteoporosis and other bone diseases.